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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
44
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pubmed:dateCreated |
2003-10-27
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pubmed:abstractText |
The mechanism by which raloxifene acts in the chemoprevention of breast cancer remains unclear. Because telomerase activity is involved in estrogen-induced carcinogenesis, we examined the effect of raloxifene on estrogen-induced up-regulation of telomerase activity in MCF-7 human breast cancer cell line. Raloxifene inhibited the induction of cell growth and telomerase activity by 17beta-estradiol (E2). Raloxifene inhibited the E2-induced expression of the human telomerase catalytic subunit (hTERT), and transient expression assays using luciferase reporter plasmids containing various fragments of the hTERT promoter showed that the estrogen-responsive element appeared to be partially responsible for the action of raloxifene. E2 induced the phosphorylation of Akt, and pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, attenuated the E2-induced increases of the telomerase activity and hTERT promoter activity. Raloxifene inhibited the E2-induced Akt phosphorylation. In addition, raloxifene also inhibited the E2-induced hTERT expression via the PI3K/Akt/NFkappaB cascade. Moreover, raloxifene also inhibited the E2-induced phosphorylation of hTERT, association of NFkappaB with hTERT, and nuclear accumulation of hTERT. These results show that raloxifene inhibited the E2-induced up-regulation of telomerase activity not only by transcriptional regulation of hTERT via an estrogen-responsive element-dependent mechanism and the PI3K/Akt/NFkappaB cascade but also by post-translational regulation via phosphorylation of hTERT and association with NFkappaB.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Raloxifene,
http://linkedlifedata.com/resource/pubmed/chemical/Telomerase
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:DuBotaoB,
pubmed-author:IgarashiHidekiH,
pubmed-author:InoueMasakiM,
pubmed-author:KawagoeJunJ,
pubmed-author:KimuraAkikoA,
pubmed-author:KurachiHirohisaH,
pubmed-author:KyoSatoruS,
pubmed-author:MabuchiSeijiS,
pubmed-author:Mori-AbeAkikoA,
pubmed-author:OhmichiMasahideM,
pubmed-author:OhshimaChikaC,
pubmed-author:OhtaTsuyoshiT,
pubmed-author:SaitohMakiM,
pubmed-author:TakahashiKazuhiroK,
pubmed-author:TakahashiToshifumiT
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
43363-72
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12917431-Breast Neoplasms,
pubmed-meshheading:12917431-Cell Division,
pubmed-meshheading:12917431-Cell Line, Tumor,
pubmed-meshheading:12917431-Cell Nucleus,
pubmed-meshheading:12917431-Chromones,
pubmed-meshheading:12917431-DNA-Binding Proteins,
pubmed-meshheading:12917431-Enzyme Inhibitors,
pubmed-meshheading:12917431-Estrogen Antagonists,
pubmed-meshheading:12917431-Estrogens,
pubmed-meshheading:12917431-Genes, Reporter,
pubmed-meshheading:12917431-Humans,
pubmed-meshheading:12917431-Luciferases,
pubmed-meshheading:12917431-Microscopy, Fluorescence,
pubmed-meshheading:12917431-Models, Biological,
pubmed-meshheading:12917431-Morpholines,
pubmed-meshheading:12917431-NF-kappa B,
pubmed-meshheading:12917431-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12917431-Phosphorylation,
pubmed-meshheading:12917431-Plasmids,
pubmed-meshheading:12917431-Promoter Regions, Genetic,
pubmed-meshheading:12917431-Protein Binding,
pubmed-meshheading:12917431-Protein Processing, Post-Translational,
pubmed-meshheading:12917431-Raloxifene,
pubmed-meshheading:12917431-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12917431-Telomerase,
pubmed-meshheading:12917431-Time Factors,
pubmed-meshheading:12917431-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Raloxifene inhibits estrogen-induced up-regulation of telomerase activity in a human breast cancer cell line.
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pubmed:affiliation |
Department of Obstetrics and Gynecology, Yamagata University, School of Medicine, Iidanishi, Yamagata, Japan.
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pubmed:publicationType |
Journal Article
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